La gestione del bambino con sospetta polmonite

Nicola Principi

DIAGNOSI DI CAP

• Sospetto diagnostico -> VALUTAZIONE CLINICA (ipofonesi plessica, modificazioni del FVT, alterazioni del MV, polipnea)

• Certezza diagnostica -> RADIOGRAFIA DEL TORACE (presenza di infiltrati alveolari o interstiziali con o senza versamento pleurico)

FREQUENZA RESPIRATORIA E PRESENZA DI CAP NEL BAMBINO

Età Frequenza respiratoria/min

< 2 mesi > 60

2 – 12 mesi > 50

> 12 mesi > 40

I dati in Tabella risultano avere una sensibilità del 74% e una specificità del 67% per la diagnosi di CAP

E’ sempre necessario eseguire la radiografia del torace per porre diagnosi di CAP?

NO nei casi di lieve o media gravità con sintomatologia clinica ben espressa

SI nei casi dubbi, per evitare inutili trattamenti antibiotici

SI nei casi gravi, per definire la situazione di partenza dell’episodio

SI nei casi inseriti in protocolli di ricerca per definire i rapporti esistenti tra le variabili in studio e i tipi di alterazione polmonare

Esposito S et al., Pediatr Infect Dis 2012

ETIOLOGY OF CAP IN FINNISH HOSPITALIZED CHILDREN

AGE

(Years)

N° VIRAL ETIOLOGY

BACTERIAL ETIOLOGY

MIXED ETIOLOGY

ALL*

<2 108 80 47 34 93

2-5 84 58 56 33 81

>5 62 37 58 19 76

TOTAL 254 62 53 30 85

*Total with detected etiology. Results expressed as percentages of patients. Adapted from Juven et al. Pediatr Infect Dis J. 2000

Episodes of Rx-confirmed CAP with viruses in children aged 13-36 months

(Esposito S et al., Influenza & Other Resp Viruses 2013)

VIRUS No.(%) *

Coinf.No.

(%)^

No. (%)*

Coinf. No.

(%)^

No. (%)*

Coinf.No.

(%)^

No. (%)*

Coinf.No.

(%)^RSV 35

(41.1)16 58 (38.6) 21 30

(30.3)10 123

(36.8)47

Rhinovirus 26 (30.5)

15 44 (29.3) 21 24 (24.2)

7 94 (28.1)

43

Bocavirus 12 (14.1)

9 15 (10.0) 11 12 (12.1)

6 39 (11.6)

26

Influenza 4 (4.7) 1 16 (10.6) 6 10 (10.1)

1 39 (11.6)

8

Metapneumo.

12 (14.1)

5 13(8.6) 4 6 (6.1) 0 31 (9.2)

9

Coronavirus

3 (3.5) 2 7 (5.8) 3 5 (5.0) 4 15 (4.5)

9

Parainfluenza (1-4)

0 (0) 0 4 (2.6) 2 6 (6.1) 2 10 (3.0)

4

Adenovirus

1 (1.1) 0 4 (2.6) 3 2 (2.0) 1 7 (2.1) 4

Episodes with viruses

68/85(80.0)

20/68 (29.4)

122/150 (81.3)

36/122 (29.5)

78/99(78.8)

14/78 (17.9)

268/334

(80.2)

70/268 (26.1)

2007-08 2008-09 Total episodes 2009-10

•% among the total number of CAP investigated; •^ % of the total number of infections in which the single virus was identified

Principal Bacteria Causing Childhood Pneumonia Principal Bacteria Causing Childhood Pneumonia (Community-Acquired Apart From the Age Group (Community-Acquired Apart From the Age Group

Birth-1 Month), by AgeBirth-1 Month), by Age

Esposito S, Cohen R, Domingo JD, Pecurariu OF, Greenberg D, Heininger U, Knuf M, Lutsar I, Principi N, Rodrigues F, Sharland M, Spoulou V, Syrogiannopoulos GA, Usonis V, Vergison A, Schaad UB. Pediatr Infect Dis J. 2012 Jun;31(6):e78-85. doi:

PNEUMOCOCCAL SEROTYPES IN CHILDREN WITH CAP AGED <5 YRS BEFORE THE USE OF PCV-13 (Esposito S et al., Pediatr Infect Dis 2012 )

4; 2.0%

14; 18.0%

5; 0%

19F; 2.0%

23F; 2.0%

3; 4.0%

6A; 2.0%

9V; 2.0%

18C; 0%

1; 2.0%

7F; 6.0%

6B; 2.0%

Not Typeable;

26.0 %

19A; 32.0%

COVERAGEPCV-7 : 28%PCV-10: 36%PCV-13: 74%

PNEUMOCOCCAL SEROTYPES IN PEDIATRIC CAP

(Resti M et al. Clin Infect Dis 2010)

CAP AND ATYPICAL BACTERIA IN 418 CHILDREN

Principi et al. Clin Infect Dis 2001%

BACTERIAL vs VIRAL PNEUMONIA

Virkki et al. Thorax 2002

N=215 Bacterial Viral % %

Alveolar infiltrates 71 29Interstitial infiltrates 48 52WBC >15 x 109/l 63 37ESR > 30 mm/h 64 36CRP > 40 mg/l 70 30CRP > 80 mg/l 75 25

ADVANTAGES AND LIMITS OF PROCALCITONIN IN CLINICAL

PRACTICE

From Gendrel D et al. Pediatr Infect Dis J 1999

6,5 y, S.pneumoniae, widespread interstitial

1,9 y, S.pneumoniae, alveolar changes

2.8 y, Rhinovirus,alveolar changes

0.3 y, parainfluenzae and HHV6, alveolar changes

BacterialVersusViralPneumonia

Virkki R et alThorax, 2002

EFFICIENCY OF RAPID DIAGNOSTIC TESTS FOR INFLUENZA VIRUSES IN

OFFICE PRACTICE

TEST DIRECTIGEN

FLU A+B

Z STAT FLU

QUICKVUE INFLUENZA

TEST

FLU OIA

COMPANY BECTON DICKINSON

ZYME TX, INC.

QUIDEL BIOSTAR

SENSITIVITY(%)

67 (T)

62 (T)

73 (N)

62 (T)

SPECIFICITY(%)

92(T)

99(T)

95-99(N)

79.5(T)

T= Throat Swab; N= Nasal Swab

Benjamin J. Contemp Pediatr 2000

TEST MICROBIOLOGICI PER LA DIAGNOSI EZIOLOGICA DI CAP

TEST VANTAGGI LIMITI

Tampone nasofaringeo

Facile esecuzione

Non correla con i dati polmonari se non per virus

e batteri atipici

Coltura dell´espettorato

Buona sensibilitá

Non attendibile nel bambino piccolo

Emocoltura Facile esecuzione

Bassa sensibilitá

Puntura polmonare

Facile esecuzione,

buona sensibilitá

Media invasivitá

Puntura cricoidea

Buona sensibilitá

Alta invasivitá

BAL Buona sensibilitá

Alta invasivitá

NASOPHARYNGEAL COLONIZATION (%) IN PNEUMONIA VS HEALTHY

CHILDREN

0

5

10

15

20

25

30

S.pneumoniae H.influenzae M.catarrhalis

Healthy Pneumonia

From Nohynek et al. Pediatr Infect Dis J 1995

RISULTATI DEL TEST RAPIDO BINAX NOW

Popolazione

Tot. con Binax NOW positivo (%)

Binax NOW pos e

colonizzaz. NF (%)

Binax NOW pos e assenza di

colonizzaz. NF (%)

Casi con IPD

5/5 (100,0)* 2/2 (100,0)* 3/3 (100,0)*

Casi senza IPD

29/150 (19,3) 16/28 (57,1)° 13/122 (10,7)

Controlli 35/200 (17,5) 26/53 (49,1)° 9/147 (6,1)

*p<0,05 vs casi senza IPD e controlli

°p<0,0001 vs casi senza IPD e controlli senza colonizzaz. NF

Esposito S et al. Pediatr Infect Dis J 2004

DIAGNOSTIC TESTS FOR M. PNEUMONIAE AND

C. PNEUMONIAE

TEST SPECIMEN COMMENTS

CULTURE Throat or NP swab, Requires tissue culture; notsputum, bronchial routinely available; requireswashing, tissue several days of incubation

PCR Throat or NP swab, No FDA-approved kits; availablesputum, bronchial from research laboratories;washing, tissue potential for rapid diagnosis

SEROLOGY Serum Paired acute-convalescentsera preferred; IgM may take up to 4-6 weeks to appear(therefore retrospective)

HOW TO TREAT PEDIATRIC CAP

The choice of empirical antibiotic treatment for

paediatric CAP should be based on diagnostic

algorithms that begin with age of the patient, and then

consider epidemiological and clinical factors (with

particular attention on severity of the disease),

vaccination status, PK/PD characteristics and finally the

results of laboratory tests and chest radiography

Esposito S et al., Pediatr Infect Dis J 2012

CHILDREN IN THE FIRST MONTH OF AGE

The traditionally used combination of ampicillin and one of the aminoglycosides (mainly gentamicin) remains the treatment of choice

As an alternative, a broad spectrum parenteral cephalosporin can be used

In cases when Listeria monocytogenes or Enterococcus sp. or anaerobes are considered, ampicillin should be included in the regimen

In critically ill patients, staphylococcal pneumonia should be considered and, in these circumstances, anti-staphylococcal penicillin or, in areas where methicillin-resistant strains of S. aureus have appeared, an active non beta-lactam agent (such as clindamycin or vancomycin) should then be added to the regimen

CHILDREN AGED 1 MONTH UP TO 3 MONTHS

S. pneumoniae is the most important aetiological agents of CAP in this age group throughout the world

A -lactam antibiotic is recommended

As in the case of neonates, in critically ill patients anti-staphylococcal antibiotic can be used

Chlamydia trachomatis and Bordetella pertussis should be considered especially in presence of little or no fever and severe cough. In such cases, macrolides are the drugs of choice

TERAPIA DELLA CAP NEL LATTANTE DI 1-3 MESI

(LIVELLO DI PROVA: 6; FORZA DELLA RACCOMANDAZIONE: B)

ASSENZA DI FEBBRE, TOSSE IMPORTANTE, INFILTRATO

INTERSTIZIALE

VEROSIMILMENTE CHLAMYDIA TRACHOMATIS E BORDETELLA PERTUSSIS

ERITROMICINA O CLARITROMICINA PER 14 GIORNI O AZITROMICINA

PER 3 GIORNI

PRESENZA DI FEBBRE, CONSOLIDAMENTO LOBARE

VEROSIMILMENTE STREPTOCOCCUS

PNEUMONIAE; RARAM. Hib E STAPHYLOCOCCUS AUREUS

AMOXICILLINA ORALE O, NEI CASI PIU’ GRAVI, CEFOTAXIMA

O CEFUROXIMA O CEFTRIAXONE EV PER 10

GIORNI

ANTIBIOTIC THERAPY OF CAP OF INFANTS AND CHILDREN > 4 MONTHS

OF AGE

STREPTOCOCCUS PNEUMONIAE AND ATYPICAL BACTERIA ARE THE MOST FREQUENT CAUSE OF CAP IN CHILDREN > 4 MONTHS OF AGE

DIFFERENTIATION OF PNEUMOCOCCAL FROM ATYPICAL BACTERIA CASES IS VERY DIFFICULT

ANTIBIOTIC THERAPY MUST COVER ALL THE MOST FREQUENT ETIOLOGIES

TERAPIA SUGGERITA NEL BAMBINO CON CAP

(4 mesi – 5 anni)AMOXICILLINA ORALE (80-90 mg/kg/die in 3 dosi)

Se la terapia sembra fallire dopo 48-72 ore, aggiungere:

ERITROMICINA ORALE (30-40 mg/kg/die in 3-4 dosi) O CLARITROMICINA (15 mg/kg/die in 2 dosi) O AZITROMICINA (10 mg/kg/die in 1 dose)

NEI CASI GRAVI USARE DA SUBITO UN BETA-LATTAMICO BETA-LATTAMASI RESISTENTE (ES. CEFALOSPORINA EV) IN ASSOCIAZIONE A UN

MACROLIDE PER OS O EV

Durata usuale della terapia: 10-14 giorniLIVELLO DI PROVA: 6; FORZA DELLA RACCOMANDAZIONE: B

ROLE OF PNEUMOCOCCAL PENICILLIN RESISTANCE ON CAP

OUTCOME (From Cardoso MRA et al., Arch Dis Child 2008)

From ECDC, 2013

TERAPIA SUGGERITA NEL BAMBINO CON CAP

(6-18 anni)ERITROMICINA ORALE (30-40 mg/kg/die in 3-4 dosi) O

CLARITROMICINA (15 mg/kg/die in 2 dosi) O AZITROMICINA (10 mg/kg/die in 1 dose)

Se la terapia sembra fallire dopo 48-72 ore, aggiungere:AMOXICILLINA ORALE (80-90 mg/kg/die in 3 dosi)

NEI CASI GRAVI USARE DA SUBITO UN BETA-LATTAMICO BETA-LATTAMASI RESISTENTE (ES. CEFALOSPORINA

EV) IN ASSOCIAZIONE A UN MACROLIDE PER OS O EVDurata usuale della terapia: 10-14 giorni

LIVELLO DI PROVA: 6; FORZA DELLA RACCOMANDAZIONE: B

TERAPIA CON VANCOMICINA DELLE POLMONITI DA IN PEDIATRIA

Nei soggetti pluritrattati e nelle aree geografiche ove la resistenza di Streptococcus pneumoniae e Staphylococcus aureus è >20%, la vancomicina è considerata il farmaco di scelta

Il dosaggio consigliato da molti anni è 40 mg/kg/die in 3-4 dosi

Recenti ricerche indicano un aumento del rischio di fallimento per aumento delle MIC

Un riferimento considerato ottimale per la previsione dell’efficacia della terapia è il trough level, vale a dire la concentrazione immediatamente precedente la dose successiva

Il trough level deve rimanere quante più volte possibile sopra 10 mg/L per avere efficacia ed evitare l’insorgere di eventi avversi

THROUGH SERUM LEVELS OF GLYCOPEPTIDES ACCORDING TO INITIAL DOSAGE (25, 40 OR 50

MG/KG/DIE) (From Ito H et al., J Infect Chemother 2013)

Drug Main finding

LinezolidIt seemed to be effective in 77.5-90.0% of children with pneumococcal bacteremia or pneumonia; few data concerning its effect on pneumococcal penicillin-resistant strains

Ceftobiprol

e

It inhibited 95% of S. pneumoniae strains, including penicillin non-susceptible strains (those with a MIC ≥4 µg/mL) and highly resistant ceftriaxone strains (those with a MIC ≥8 µg/mL)

CeftarolineIt had greater in vitro activity (MIC=0.5 µg/mL) than penicillin, cefotaxime or ceftriaxone (MIC=8 for all the comparators)

NEW DRUGS FOR THE TREATMENT OF PNEUMOCOCCAL INFECTIONS WITH

INTERESTING PRELIMINARY RESULTS (From Esposito S & Principi N. Expert Opinion

Pharmacotherapy 2013)

Antibiotic (Ab) exposure by treatment group and CAP severity

(From Esposito S et al., Respir Med 2011)

• Repeated chest radiographs Repeated chest radiographs should be obtained in children should be obtained in children who fail to demonstrate clinical improvement and in those who fail to demonstrate clinical improvement and in those who have progressive symptoms or clinical deterioration who have progressive symptoms or clinical deterioration within 48–72 hours after initiation of antibiotic therapy within 48–72 hours after initiation of antibiotic therapy (strong recommendation; moderate-quality evidence)(strong recommendation; moderate-quality evidence)

• Routine daily chest radiography is not recommended in Routine daily chest radiography is not recommended in children with pneumonia complicated by parapneumonic children with pneumonia complicated by parapneumonic effusion after chest tube placement or after videoassisted effusion after chest tube placement or after videoassisted thoracoscopic surgery (VATS), if they remain clinically thoracoscopic surgery (VATS), if they remain clinically stable (strong recommendation; low-quality evidence)stable (strong recommendation; low-quality evidence)

• Follow-up chest radiographsFollow-up chest radiographs should be obtained in patients should be obtained in patients with complicated pneumonia with worsening respiratory with complicated pneumonia with worsening respiratory distress or clinical instability, or in those with persistent distress or clinical instability, or in those with persistent fever that is not responding to therapy over 48-72 hours fever that is not responding to therapy over 48-72 hours (strong recommendation; low-quality evidence))(strong recommendation; low-quality evidence))

Chest RadiographyChest Radiography

IDSA guidelines; CID 2011. Kindly proded by Prof. Greenberg