Episode 165: Early-Onset Sepsis Part 2 Dr. Lovedip Kooner explains how to use the Kaiser Permanente early-onset sepsis calculator and explains other useful tools to assist in the diagnosis of EOS. Dr. Arreaza adds comments about the usefulness of this calculator Written by Lovedip Kooner, MD. Comments and editing by Hector Arreaza, MD.
Episode 165: Early-Onset Sepsis Part 2
Dr. Lovedip Kooner explains how to use the Kaiser Permanente early-onset sepsis calculator and explains other useful tools to assist in the diagnosis of EOS. Dr. Arreaza adds comments about the usefulness of this calculator
Written by Lovedip Kooner, MD. Comments and editing by Hector Arreaza, MD.
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Introduction: As a recap, Early-onset sepsis is diagnosed within 72 hours (or within 7 days, according to some experts) after birth. We talked about GBS as the main culprit of EOS. 28% of EOS by GBS are babies born <37 weeks of age and the mortality rate is 19% at that age. Term infant mortality is 2%. EOS has decreased from 0.37 cases per 1,000 live births in 2006 to 0.23 cases per 1,000 live births in 2015. An interesting fact is that meningitis is diagnosed in 10% of babies with EOS, and 9% of those babies do not have bacteremia. But today we are going to dig deeper into the management by using online tools, particularly the Kaiser Permanente Neonatal EOS calculator.
Using the Kaiser Permanente (KP) neonatal EOS calculator.
Lovedip: It is a multivariate risk assessment tool that guides us in the management of neonatal early-onset sepsis. The Kaiser Permanente (KP) neonatal EOS calculator combines 2 predictive models. One model is based on risk factors known at birth and the other model is based on the newborn clinical condition during the early hours after birth.
The risk factors are: gestational age, highest maternal antepartum temperature, maternal GBS status, duration of rupture of membranes, and antibiotics (type and duration). If that sounds familiar, it is. It’s mostly the same information used in the categorical risk assessment, except substituting maternal highest antepartum temperature for chorioamnionitis diagnosis. This information is input into the calculator and two values are obtained. The first value is the EOS risk at birth, the second value is the EOS risk after the clinical exam. The clinical exam is broken down into well-appearing, equivocal, and clinical illness.
The well-appearing baby in general is described as alert and consolable, moving all extremities, good skin color no bruising, except possibly acrocyanosis, hungry and when put on mom’s breast will attempt to suckle, normal vital signs, good reflexes like Moro and grasp, tends to have flexed limbs, especially arms, regards faces but no tracking. In a previous episode, we mentioned that hypoglycemia is not a good indicator of EOS caused by GBS. Let’s talk about the criteria for a well-appearing baby in the Kaiser Permanente tool.
Well-appearing for the purposes of the KP calculator means no persistent physiologic abnormalities.
Equivocal means: “Tachy, Tachy, Temp, Resp”
Note: abnormality can be intermittent.
An ill newborn, in general, is described as having abnormal vital signs, either hyper or hypothermia, tachycardia, bradycardia or arrhythmia, flaccid, doesn’t regard faces, no or muted reflexes and poor suck, mottled color, cyanosis or bruising, petechiae, retractions, nasal flair or poor nasal breathing (with choanal atresia, pinks up only when crying), gasping respirations, poor bowel sounds, possibly distended OR scaphoid (with atresias will have scaphoid abdomen and with anomalies like TEF depending on type, emesis or difficulty breathing when fed) obvious congenital anomalies, etc.
Clinical Illness in the Kaiser Permanentetool is defined as:
After all that information is entered into the Kaiser Permanente calculator, the options for management are clinical monitoring, laboratory evaluation, or antibiotic administration.
Example:
-Incidence: 0.5/1,000 live births
-Gestational age: 36 6/7 weeks
-Highest maternal antepartum temperature: 102 F
-ROM: 5 hours
-Maternal GBS: Positive
-Intrapartum antibiotics: Broad spectrum 3 hours prior to birth
-RESULT: EOS risk at birth 2.34.
Recommendations based on physical exam:
1. Well-appearing baby, risk 0.96, RECOMMENDATIONS: No culture, no antibiotics, vitals every 4 hours for 24 hours.
2. Equivocal, risk 11.61, RECOMMENDATIONS: Start empiric antibiotics and vitals per NICU.
3. Clinical Illness, risk 47.46, RECOMMENDATIONS: Start empiric antibiotics and vitals per NICU.
The Kaiser Permanente neonatal early-onset sepsis calculator was analyzed in a meta-analysis, as published in the American Family Physician in 2021. Six high-quality, non-randomized controlled trials were evaluated, including more than 170,000 neonates. The calculator was compared to the standard approach recommended by the CDC guidelines.
The analysis showed there was a statistically significant reduction in antibiotic use, a reduction in the number of laboratory tests, and a reduction in NICU admission in neonates who were managed following the sepsis calculator compared with the standard approach.
There was no difference in readmission rates to NICU and no difference in culture-positive sepsis between neonates treated using the sepsis calculator and those treated with the standard approach. In summary, I recommend using the Kaiser Permanente calculator as part of your evaluation. BTW, I received no money from KP. It is important to know that depending on resources and institutional policies, your management may change.
Use of CBC and CRP.
CBC interpretation in neonates: Remember that CBC in newborns needs to be evaluated following the normal parameters for neonates. For example, WBC up to 30,000 per mm3, and hemoglobin up to 19.9 gm/dL can be normal in neonates.
Serial white blood cell counts and immature–to–total neutrophil ratio (I/T ratio) generally greater than or equal to 0.2 by some experts is considered positive for sepsis. Complete blood cell counts taken 12-24 hours after birth are associated with increased sensitivity and negative predictive value compared to a sample taken 1-7 hours after birth.
C-reactive protein (CRP) is also often used and it rises within 6 hours of infection and peaks at 24 hours. Two normal CRP levels, one taken between 8-24 hours of age and the second 24 hours later, have an over 99% negative predictive value. Single values of CRP or procalcitonin obtained after birth to assess the risk of EOS are neither sensitive nor specific to guide EOS care decisions.
Procalcitonin: Procalcitonin may be difficult to interpret within the first 3 days after birth due to elevations caused by noninfectious etiologies and the physiologic rise after birth. It is important to note that neither single values of CRP nor procalcitonin after birth should be used to guide the management plan of infants undergoing evaluation for EOS>.
Extreme values in CBC: Extreme values (total WBC count <5000/μL [I/T >0.3; ANC <2000/ μL] in one study and WBC count <1000/μL [ANC <100/μL; and I/T >0.5] in the other) were associated with the highest likelihood ratios but very low sensitivities.
Cultures/lab tests: Culture results are used to confirm suspected sepsis. You must not wait for the result to start treatment with empiric, broad-spectrum antibiotics in newborns suspected to have EOS.
Treatment:
The recommended empirical antibiotic regimen for most at-risk infants for Early-Onset Sepsis involves combining ampicillin and gentamicin. In the case of critically ill term infants, the empirical use of additional broad-spectrum agents may be warranted until culture results are available and an appropriate treatment plan can be determined.
In areas with E. coli highly resistant to ampicillin, carbapenem should be considered.
When blood cultures are sterile, antibiotic therapy should be discontinued by 36 to 48 hours of incubation unless there is clear evidence of site-specific infection.
Why not treat everyone with antibiotics?
Unneeded antibiotics can cause changes in the GI flora (needed for vitamin K ) and disturb the whole gut colonization with healthy bacterial flora, this can have an impact on the newborn’s kidney if dosage is not corrected (Harriet Lane Handbook gives neonatal doses) because GFR is lower in neonates, and side effects are always possible. In the neonatal nursery, the emergence of resistant bacteria is always a worry.
Antibiotic resistance is one of the most feared threats to humanity. In retrospective studies primarily focused on term infants, researchers have associated early antibiotic administration with elevated risks of various health issues in later childhood, including wheezing, asthma, food allergy, inflammatory bowel disease, and childhood obesity.
Take home points:
(1) Understand how to assess a newborn infant’s risk of EOS.
(2) Understand how to determine which steps should be taken at particular levels of risk, including the timely administration of empirical, broad-spectrum antibiotic therapy.
(3) Understand how to decide when to discontinue empirical antibiotic therapy.
(4) Consistently normal values of CRP and procalcitonin over the first 48 hours of age are associated with the absence of EOS, but serial abnormal values alone should not be used to decide whether to administer antibiotics in the absence of culture-confirmed infection.
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Conclusion: Now we conclude episode number 165, “Early Onset Sepsis Part 2.” Dr. Kooner explained the elements of the Kaiser Permanente Early Onset Sepsis calculator available online for free. Dr. Arreaza provided insights on the usefulness of this tool. Some other markers, such as CBC, CRP, and procalcitonin were also explained.
This week we thank Hector Arreaza, Lovedip Kooner, and Katherine Schlaerth. Audio editing by Adrianne Silva.
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