Sepsis Literature Review
Guidelines for management of well-appearing infants and children with fever without a source (FWS) in the post-pneumococcal vaccine era
(Adapted from: Baraff, LJ. Management of fever without source in infants and children. Annals of Emergency Medicine 2000; 36(6) 602-614)
Birth to 1 month, T>38
Evidence
* Chance of SBI in infants <28 days with T>38= 4-12%
* UTI in these young infants is associated with a 15-20% risk of bacteremia
* Even well-appearing infants in this age group may have SBI. Clinical exam is unreliable and viral symptoms are not considered a source for the fever
Recommendations
* CBC, blood culture, urine culture, LP, antibiotics (ampicillin and gentamycin IV, or ampicillin and cefotaxime IM).
* Most guidelines recommend admitting febrile infants in this age group regardless of lab results.
* In some cases outpatient management may be acceptable in low-risk patients (WBC<15 and >5, U/A normal, well-appearing) with very close follow up.
Back to top
1-3 months, T>38
Evidence
* Lab results can be used to divide febrile infants of this age group in "high-risk" and "low-risk" for SBI based on total WBC count.
* Multiple studies have established that the chance of SBI(not including UTI) in "low-risk" infants (WBC<15K) is 2-3%. The risk is even less than that if one study that used WBC of <20 as low risk is excluded (~1%)
* Preliminary PROS (Pediatric Research in Office Settings) study data shows that, in a closely followed, predominantly white population, lack of adherence to guidelines was NOT accompanied with higher rates of SBI, or worse outcomes.
Recommendations
* UA and urine culture on all infants. If UA is positive, begin treatment for pyelonephritis and consider admission (prevalence of UTI in febrile infants in this age group is about 9% overall: 20% in uncircumcised boys, 12% in girls and 2% in circumcised boys (3)
* CBC in all infants
* Blood cx and abx (ceftriaxone IM or IV) if WBC >15
* Lumbar puncture in any irritable or lethargic child, and strongly consider if antibiotics are to be given
* Follow up as outpatient the next day if antibiotics are given, admit if unable to assure follow up.
Back to top
3-36 months, T>39, unvaccinated against pneumococcus
Evidence
Occult bacteremia
* Overall risk of occult bacteremia in well-appearing children with FWS with temp >39 without WBC criteria is 2.6-6% (mean 2.8%)
* Combined results of two large RCTs shows a risk of occult pneumococcal bacteremia in children with T>39.5 of 10% in those with WBC>15K, and 1% in those with WBC<15K squared
Meningitis
* Risk of pneumococcal meningitis in untreated children with occult bacteremia is 3% - therefore the risk of pneumococcal meningitis in the higher risk group is ~ .3%, risk in the low risk group is ~ .03%
UTI
* UTIs are common in girls of this age group, found in 6-8% of girls <12 months of age. For boys, the risk is 2.7% in boys under 6 months of age, primarily uncircumcised.
* Prevalence overall in girls <24 months is 10%.
* Risk is very low (<1%) in circumsized boys greater than 3 months of age,and all boys greater than 6 months of age.
Recommendations
* U/A and urine culture if T>39 for all girls <24 months and uncircumcised boys <6 months. Consider in circumcised boys <6 months and uncircumcised boys 6-12 months.
* If the U/A suggests UTI, begin outpatient treatment for pyelonephritis (first dose of antibiotics should be given in clinic/ER: ceftriaxone IM or cefixime po)
* U/A alone can be used to screen for UTI in children > 12 months, circumcised boys >6 months
* CBC if T>39.5
* Blood culture and antibiotics (ceftriaxone IM/IV) if WBC >15
* Close outpatient follow up
* LP if child is irritable or lethargic, and strongly consider prior to giving antibiotics
Back to top
3-36 months, T>39, vaccinated against pneumococcus
Evidence
* The 7-valent pneumococcal vaccine was tested in a large Kaiser-based randomized controlled trial of 37,000 children, showing 97.4% efficacy against invasive pneumococcal disease in fully vaccinated children, (including the booster) and 89.1% efficacy overall, after the primary series (2,4,6 months) of vaccinations (3)
* In the 18,000 unvaccinated children, there were 55 cases of invasive pneumococcal disease (a comparable rate to the RCTs mentioned above). Only 6 cases occurred in the 18,000 vaccinated children, a 90% reduction in cases
* Approximately 85- 97% of pneumococcal isolates that cause occult bacteremia are represented in the heptavalent vaccine.(5) The vaccine, therefore, should lower rates of invasive pneumococcal disease by nearly 90%, making the risk <1% for all children, regardless of WBC count.
* Efficacy of the vaccine after 2 doses is unclear at the moment due to lack of sufficient data, but the Kaiser study results suggest that immunity against invasive disease is good between dose 2 and 3, as long as the child receives dose 3 promptly (data from otitis media, a much more common disease, suggests that immunity falls off after 7 months of age if the 3rd dose is not given)
* Current vaccination schedule recommends 4 doses given at 2,4,6 and 12-15 months, with catch up schedules for older children up to 2 years of age.
Recommendations
* Screen for UTI as above, for T>39
* No blood tests or antibiotics necessary in well-appearing child who has received 3 doses of prevnar, or is within 2 months of the 2nd dose.
Back to top
Who Gets What?
Who gets CBC and blood cultures?
* Age <3 months, T>38
* Age 3-36 months, T>39.5, unvaccinated (ie: less than 2 doses) against pneumococcus
Who gets U/A and culture?
* Age <3 months, T>38
* Girls 3-24 months, T>39
* Circumsized boys 3- 6months, T>39
* Uncircumsized boys 3-12 months, T>39
Who gets LP?
* Any lethargic or irritable child, of any age, with T>38
* Age <1 month, T>38
* Age 1-3 months, T>38, strongly consider prior to giving antibiotics
* Age 3-36 months, T>39 strongly consider prior to giving antibiotics
Who gets antibiotics?
* Any toxic-appearing child (amp/gent IV or ceftriaxone IV, consider adding vancomycin for S. pneumo coverage)
* Age < 1 month, T>38 (amp/gent IV or amp/cefotaxime IV)
* Age 1-3 months, T>38, WBC count >15 or <5, or U/A positive for leukocyte esterase or nitrites (ceftriaxone IM/IV)
* Age 3-36 months, T>39, U/A positive for leuk esterase or nitrites (outpatient po antibiotics OK, give first dose IM/po)
* Age 3-36 months, T>39.5, unvaccinated (ie: less than 2 doses) against pneumococcus, WBC>15 (ceftriaxone IM/IV)
Developed by:
Pediatric Hospitalist Group
Andree Hest, R.PH., MScPharm
Bing Tschai, R.N., CNS
Oded Herbsman, M.D.
Alan Johnson, M.D.
David Tejeda, M.D.
Back to top