1. Community-acquired pneumonia in children
Vojko Berce
Division of Pediatrics, University Medical Centre and Faculty of Medicine Maribor
Slovenia

2. Pneumonia - definitions
Inflammation of lung parenchyma because of air-borne or haematogenous infection
WHO: cough and dyspnoea + tachypnea
Most of definitions does not require imaging diagnostics
Uncomplicated CAP: alveolar infiltrate limited to one lobe, bronchopneumonia, interstitial pneumonia
Complicated CAP: pleural effusion, multilobar pneumonia, pulmonary abscess, empyema, pneumothorax
Fever
signs/symptoms from respiratory tract (cough, respiratory distress, chest pain)
Signs of affection of lung parencyhma (imaging method or auscultation)

3. COMMON BACTERIAL
RARE BACTERIAL
Cause
Characteristic
Streptococcus pneumoniae
Alveolar consolidation (CXR), effusion, empyema
Haemophilus influenzae type B
Non-vaccinated
Group B beta-haemolytic streptococcus
Neonates
Staphylococcus aureus
After the flu, pneumatocele, empyema,
Group A beta-haemolytic streptococcus
Empyema
Moraxella catarrhalis
Mycoplasma pneumoniae
Both together represent the most common cause of CAP in school-children
Neisseria meningitidis
Chlamydophila pneumoniae
Chlamydophila psittaci
Bird owners
Chlamydia trachomatis
Infants (1-3 months)
Coxiella burnetii
Q fever, farmers (sheep)
Anaerobes
Aspiration pneumonia
Legionella species
Contaminated water
Gram negative bacteria
Nosocomial pneumonia
Ureaplasma urealyticum
Afebrile pneumonia in neonates
Haemophilus influenzae – nontypeable

4. COMMON VIRAL
RARE VIRAL
Cause
Charasteristics
Characteristics
RSV
Bronchiolitis/pneumonia
Rhinovirus
Symptoms of cold
Human metapneumovirus
Similar to RSV
Enterovirus
neonates
Parainfluenza type 1-3
Laryngitis
Herpes simplex
Influenza A, B
High fever, winter outbreak
Cytomegalovirus
Infants (afebrile pneumonia syndrome), immune deficiency
Bocavirus
Adenovirus
Severe pneumonia
Measles
rash
Rhinovirus?
Varicella
Viruses (RSV) are more common cause of CAP in small children (<3 years) compared to bacteria
Moulds (Pneumocystis jiroveci, Aspergillus), Helmints (Ascaris, Toxocara, Strongyloides)
Mycobacteriae (TBC in non-tuberculosis)

5. Clinical and laboratory characteristics
Etiology
Clinical and laboratory characteristics
Bacterial pneumonia (Streptococcus pneumoniae)
All ages
Sudden onset with high fever, chills (“toxic appearing”), tachypnea, often without respiratory distress
Chest (abdomen) pain
Localized phenomena on auscultation (crackles, diminished breath sounds, bronchial breathing)
Clinical signs often absent in small children (fever without a focus)
Leukocytosis (>15.000)
CXR: alveolar infiltrate – consolidation (lobar, segmental, round), pleural effusion (50%)
Atypical bacteria (Mycoplasma pneumoniae, Chlamydophila pneumoniae)
School-children and adolescents
Systemic signs (malaise, myalgia, headache, photophobia, sore throat, rash) then gradual appearance of dry cough
Low-grade fever
Crackles ± wheeze (often unilateral)
Extra-pulmonary complications (Stevens-Johnson syndrom, hemolytic anemia, hepatitis, encephalitis)
CXR: bronchopneumonia, interstitial infiltrates, pseudoconsolidation, small effusion (20%)
Viruses
Preschool children
Gradual onset with signs of cold and cough (from the beginning)
Signs of respiratory distress
Bilateral phenomena on auscultation (crackles ± wheeze)
Conjunctivitis, rash, diarrhea
CXR: bilateral interstitial infiltrates

6. BPN
ALVEOLAR INFILTRATE
INTERSTITIAL INFILTRATE

7. Poor diferentiation between the causes of CAP
WBC < → good negative predictive value for bacterial CAP
Useful for monitoring the effect of therapy
↓CRP at the onset of bacterial CAP, ↑CRP with some viruses and Mycoplasma

8. Blood culture positive in less than 10% of bacterial CAP
Detection of genome (PCR) of respiratory viruses and atypical bacteria from naso-pharynx
Culture of sputum (> 5 years) only weakly reflects the infection in lower airways
Blood culture positive in less than 10% of bacterial CAP
Seroconversion (IgM) to Mycoplasma pneumoniae only after 1 week of illness

9. Sensitivity of all isolates of Streptoccocus pneumoniae in Slovenia - 2015
National laboratory for health, food and environment

10. Antibiotic treatment of CAP in children – Slovenian national guidelines/recommendations (Čižman M. Beovič B. Kako predpisujemo antibiotike v bolnišnicah)
AGE AND PROBABLE ETIOLOGY
ANTIBIOTIC
Daily dose (mg/kg/day or IE/kg/day): number of daily doses
4 months to 5 years, probable bacterial – outpatient treatment
amoxicillin (drug of choice)
45: 3 peroral
penicillin V (alternative)
– IE: 3 peroral
4 months to 5 years, probable bacterial – severe course (hospital)
penicillin G (drug of choice)
– IE: 4 iv
amoxicillin+clavulanic acid (alternative)
100 (amoxicillin): 4 iv
5–18 years, probable atypical bacteria – outpatient treatment
azithromycin or
 clarithromycin
10: 1 first day, then 5: 1 for 4 day peroral
15: 2 peroral
5–18 years, probable bacterial - outpatient
penicillin V or
amoxicillin
5–18 years, probable bacterial – severe course (hospitall)
penicilin G or
amoxiclilin+clavulanic acid
– : 4 iv
cefotaxime (CAP with complications – pleural effusion)
150: 3 iv
Bacterial pneumonia – allergy to penicillin
Cefotaxime?, Clindamycin?, Quinolones?

11. Antibiotic treatment of CAP in children - Slovenian national guidelines/recommendations
Severe course of CAP or CAP after the flu → combination of antistaphylococcal penicillin and third generation of cephalosporin
Duration of treatment 7-10 dni in preschool children, 5-7 dni in schoolchildren (at least 3 days without fever)
Penicillin can be prescribed in children who received at least 3 dosed of HiB vaccine (otherwise amoxicillin)
Hospital treatment: parenteral antibiotic 1-2 days, when 24 hours afebrile → shift to peroral treatment
Čižman M. Beovič B. Kako predpisujemo protimikrobna zdravila v bolnišnicah. Ljubljana 2013

12. STUDY Aims Participants Methods
to compare the clinical and laboratory characteristic of different types of CAP (viral, atypical, bacterial),
to compare the sensitivity of lung ultrasound (LUS) and chest X-ray (CXR) for detecting CAP
to analyze the compliance of antibiotic treatment of CAP with Slovenian national guidelines.
Aims
166 children with CAP, hospitalized at Clinic of Pediatrics, Maribor ( – )
Previously healthy, age 3 months – 18 years, no ICU
Pneumonia detected with CXR and/or ultrasound
Stratification into bacterial, atypical and viral CAP groups (infiltrates, microbiological and laboratory results
Participants
Chest x-ray and lung ultrasound
NF swab - PCR based diagnostics of respiratory viruses and atypical bacteria
Blood culture, sputum
CRP, WBC
Antibiotic treatment on the first and third day
Methods

13. STUDY - RESULTS Mycoplasma pneumonie – 30 subjects
77 (46.4%)
89 (53.6%)
Mean age 4.4 years
Mycoplasma pneumonie – 30 subjects
Chlamydophilia pneumoniae – 2 subjects
Probably viral CAP – 54 subjects
Probably bacterial CAP – 80 subjects
19 (11.4%) subjects already received antibiotic treatment before the admission.
In the first 24 hours of hospitalization antibiotic therapy was administered to 147 (88.6 %) children with CAP.

14. RESULTS - clinical and laboratory characteristics
Characteristic [% (n)]
Bacterial
Atypical
Viral p
Chest/abdominal pain
51.2 (41)
18.8 (6)
7.4 (4)
< 0.01
Crackles on auscultation
20.0 (16)
84.4 (27)
74.1 (40)
Wheezes on auscultation
5.0 (4)
28.1 (9)
48.1 (26)
Respiratory distress
15.0 (12)
31.2 (10)
59.3 (32)
Diminished breath sounds
27.5 (22)
21.9 (7)
18.5 (10)
0.47
Signs of lung consolidation
21.3 (17)
15.6 (5)
<0.01
Need of additional oxygen
6.3 (5)
38.9 (21)
Characteristic (mean)
Age (years)
3,5
7.9
3.4
WBC3 (×109/l)
26,6
12.7
15.5
CRP (mg/dl)
169.1
47.7
73.9

15. RESULTS – lung ultrasound
Pneumonic infiltrates were detected with CXR in 137 (82.5 %) of subjects and with LUS in 161 (97.0 %) of subjects (p<0.01).

16. RESULTS - antibiotic day 1.→ day 3.
ANTIBIOTIC THERAPY
(Probable) etiology
SUMMARY
bacteria
atypical (Myc + Chl)
viruses
amoxicillin+clavulanic acid
27 → 32
4 → 1
22→18
53 → 51
penicillin
26 → 31
5 → 2
7 → 5
38 → 38
azithromycin
6 → 4
13 →26
9 → 6
28 → 36
cefuroxime
4 → 3
1 → 1
6 → 5
ceftriaxone
2 → 5
0 → 0
3 → 6
penicillin and azithromycin
8 → 4
3 → 1
12 → 6
amoxicilin+clavulanic and azithromycin
1 → 1
2 → 1
6 → 3
amoxicillin+clavulanic and gentamycin
1 → 0
no antibiotic therapy
5 → 0
3 → 0
11→21
19 → 21 80 32 54
166

17. Discussion - limitations
Lack of „gold standard“ for determination of etiology of CAP in children
Isolation of microbes from upper airways only weakly reflects the cause of inflammation in lower airways (asymptomatic shedding or colonisation of viruses and Mycoplasma in NF)
Bacterial CAP as superinfection of viral RTI
Insensitive (blood culture) or unfeasible (sputum < 5 years) tests for bacterial CAP
Recommendations for antibiotic treatment limited to countries with good susceptibility of pneumococci to penicillin

18. Discussion – clinical characteristics
Chest/abdominal pain
Normal auscultation
Bacterial CAP
Respiratory distress
Bilateral phenomena (crackles ± wheeze) on auscultation
Viral pneumonia
Older children
Unilateral crakles
Atypical bacterial CAP

19. Discussion – antibiotic treatment
We followed the national guidelines for antibiotic treatment of CAP
Results of microbiological investigations did not reduce the proportion of children treated with antibiotic (day 3)
Microbiological investigations guided the adjustment of therapy in atypical bacterial pneumonia
In most children with proven viral infection we did not abolish the antibiotic therapy

20. Conclusion
Combination of epidemiologic, clinical and laboratory parameters helps to define the etiology of CAP even in the settings with limited diagnostic possibilities
Lung ultrasound becomes sensitive, harmless and widely available bed-side tool for the detection of pneumonia in children and can replace the chest x-ray