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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 | 1-3 months, T>38 | 3-36 months, T>39, unvaccinated against pneumococcus | 3-36 months, T>39, vaccinated against pneumococcus | Who Gets What?

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.

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.

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

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.

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.

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