JOURNAL READ

31/10/2022
 Introduction
• Sepsis and CNS infections are severe complications in the neonatal and infant period.
• Despite ongoing advances in neonatal care, the prevalence of neurological sequelae following neonatal
CNS infections remains high.
• According to the Annual Report of the Netherlands Reference Laboratory for Bacterial Meningitis of the
Amsterdam University Medical Centre and the National Institute of Public Health and the Environment
(RIVM), the 2015 and 2016 incidence of neonatal CNS infection in the Netherlands has been 0.3 cases
per 1000 live births .
• This is comparable with the UK and Ireland where the incidence is estimated at 0.38 per 1000 live births.
• One of the severe short-term complications of CNS infection is inflammation of the ventricular system
or ventriculitis.
 Objectives
• With this study, we aim to explore and describe the entity of ventriculitis.
• We aim for comparison between CNS infections with and without
ventriculitis regarding clinical, microbiology and ultrasonographic
characteristics.
• Furthermore, we aim to retrospectively review all available ultrasound imaging
results
 Study design
• Study Design: Retrospective cohort study
• Study Duration: between 2004 and 2016
• Study Population: 124 patients
• The study compared patients’ CNS infections with signs of ventriculitis and CNS infections without
ventriculitis.
-Data regarding birth conditions, comorbidities, symptoms and timing of diagnosis, illness severity,
required support, complications and laboratory results were collected from the hospital information
system and subsequently analysed.
• Inclusion criteria: Culture-proven CNS infection
• Exclusion criteria: Contaminated CSF cultures (false positive)
• For comparison between proportions in the meningitis and ventriculitis groups: Two-
sided Fisher Exact test was used.
• To compare means in the laboratory results, an independent samples t-test was used.
• To assess the differences between ultrasound findings of the specified time points
(comparing CUS1 with CUS2 and CUS2 with CUS3), the Pearson Chi-square test was
used.
• To evaluate the measure of agreement between the reviewing radiologists reports with
the primary diagnosis (dichotomic diagnosis ventriculitis: Yes/No) : Cohen’s kappa (k)
was calculated. A k < 0 reflects ‘poor’, 0 to 0.20 ‘slight’, 0.21 to 0.4 ‘fair’, 0.41 to 0.60
‘moderate’, 0.61 to 0.8 ‘substantial’ and above 0.81 ‘almost perfect agreement’.
• To further assess interrater agreement, we determined the intra-class correlation (ICC).
The ICC assesses rating reliability by comparing the variability of different ratings of the
same subject to the total variation across all ratings and all subjects.
• In our cohort the raters were fixed and subject a random sample. We therefore assessed
the ICC with a two-way mixed model for absolute agreement.
 results
1. Total of 287 children meeting the inclusion criteria were admitted to the 10 hospitals
2. Mean age was 19.82 months with a median of 9.82 months .
3. The mean length of hospital stay was 4.9 (SD: 3.5) days.
4. 10 patients (3.5%) required admission to the PICU, 1 : no ventilation support, 3 : invasive mechanical
ventilation and 6 : noninvasive ventilation. No patient died.
5. Mean maximal temperature after admission was 38.8°C (SD: 0.8)
6. Chest radiographs were performed in 169 children (59%), being abnormal in 118 children (70%).
7. 140 children received antibiotic during admission (49%) and 116 presented with hypoxemia (40%).
8. Only 4 patients (4.3%) presented side effects attributed to medication, 1 patient had urticaria and 3
experienced vomiting.
 RESULTS
PATIENT
- Total n= 222
20 excluded ( 1 aged >18y/o, 7 discharged, 3
transferred out, 9 incomplete data)
PICU MORTALITY = 30.2%(n=61/202)
Median length of PICU stay= 4(IQR 2-8) days
68.3% infants
* Weak correlation between age and
PIM2(r=0.197, P=0.005), mortality
(r=0.1888,P=0.007)
Severe sepsis, n = 200(99%)
GRAM POSITIVE BACTERIA , n=60(29.7%)
GRAM NEGATIVE BACTERIA, n=34(16.85%)
Mycoplasma, n=8(4%)
CULTURE NEGATIVE, n=100(49.5%)
Viral DNA detected, n=10(5%)
Anti-virus IgM detected, n=5(2.5%)
AKI 17.8%( n= 36)
-23 patients developed AKI& fluid overload
during first 7 days after PICU admission
-8 patients diagnosed AKI prior to occurrence of
fluid overload
-3 patients occurred fluid poverload prior to
AKI diagnosis
-12 Patients diagnosed AKI and fluid overload
on the same day
 Results
1. A total of 93 children (32.6%) were treated with oseltamivir within the first 48 hours of
admission.
2. When stratified by age (under and over 12 months), these differences are more pronounced for
older children who spent total days of fever, when comparing treated versus untreated (P <
0.001). But Did not shorten the duration of fever after admission, duration of oxygen therapy or
length of stay (Table 1).
3. Older children presented more bacterial complications than younger ones (38.7% versus 6%, P <
0.0001) - NO differences in the diagnosis of bacterial complications as defined between treated
and untreated patients (6.1% versus 6.3%)
No statistically significance ( p>
0.05) for Treated vs Untreated for :
1. Days of fever after admission
2. Length of stay
3. Days of hypoxia
4. Intensive admission
5. Antibiotic prescription
 Discussion by authors
1. OTHERWISE HEALTHY children hospitalized with confirmed influenza infection did not
improve their outcome in terms of duration of fever, duration of hypoxia, length of stay,
admission to PICU or bacterial complications when treated with oseltamivir in the first 48
hours after admission.
2. CDC 2013 guideline – only approve EMERGENCY usage of oseltamivir in <1 year old
children
3. difficult to evaluate the effectiveness of oseltamivir in a hospital setting because the criteria
for admission in the available studies are heterogeneous.
4. Now, only neuraminidase inhibitors are recommended for the treatment of influenza
infections.
5. In recent observational pediatric studies, more oseltamivir resistance (up to 27%) have been
reported. rational use of antiviral drugs in otherwise healthy children without risk factors and
mild disease may help to avoid the potential spread of resistant viruses
6. HARD to justify the treatment for all children admitted for influenza without other
 Limitations IDENTIFIED BY AUTHORS

• Only analyses fever as a symptom, but does not take into

account cough or runny nose
• Do not differentiate the type of influenza virus, A or B; some
studies suggest that there could be a better response to
treatment with antiviral therapy in influenza A. (Hard to
differentiate – best benefit start within 48 hours - Peltola et al
shows clinical diagnosis accuracy for influenza 32-38%)
 Discussion by presenter - for our practise

1. Consider doing local epidemiological studies of respiratory viruses

prevalence, since oseltamivir only useful for Influenza virus
2. Clinical Suspicion + PICU admission / Underlying Chronic illnesses (except
asthma) : Strongly suggest
3. Mild symptoms + presentation > 48 hours @ hospital stay > 72 hours = Not
suggested
4. Good to know : other antiviral : inhaled zanamivir >5yo, amantadine ,
rimantadine
5. Of course a larger , multicenter Level 1 study should be anticipated
 references
• Oseltamivir for influenza in adults and children: systematic review of clinical study reports and
summary of regulatory comments BMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g2545 
• Heinonen S, Silvennoinen H, Lehtinen P, et al. Early oseltamivir treatment of influenza in children 1–3
years of age: a randomized controlled trial. Clin Infect Dis. 2010;51:887–894.
• Wang K, Shun-Shin M, Gill P, et al. Neuraminidase inhibitors for preventing and treating influenza in
children. Cochrane Database Syst Rev. 2012;1:CD002744.
• Centers for Disease Control and Prevention (CDC). Emergency Use Authorization of Tamiflu (oseltamivir).
Available at: http://www.cdc. gov/ h1n1flu/eua/tamiflu.htm. Accessed February 2, 2013.
• American Academy of Pediatrics. Committee on Infectious Diseases. Policy statement—recommendations
for prevention and control of influenza in children, 2010–2011. Pediatrics. 2010;126:816–826.