novità nella terapia delle malattie respiratorie novembre 2014
TRANSCRIPT
Francesca Santamaria Dipartimento di Scienze Mediche Traslazionali
Novità nella Terapia delle Malattie Respiratorie
Novembre 2014
Novità nella Terapia delle Malattie Respiratorie
• Wheezing
prescolare
• Tosse
• Infezioni
• Wheezing
prescolare
Wheezingepisodico
virale
Wheezing da fattori multipli
Mantenimento consigliato sempre un trial terapeutico, sospendere se inefficace
Antileucotrienico, oppure CSI, oppure
CSI + antileucotrienico
CSI (es. beclometasone equivalente 400 μg/die per 3 mesi)se sintomi persistenti:
CSI + antileucotrienico
Wheezing in età prescolare: terapia
© 2013 PROGETTO LIBRA • www.ginasma.it Brand Eur Respir J. 2014
OR for long-term ICS and/or leukotriene modifiers prescription
7.1
2.2 2.7
8.5
Frequent wheeze ED visits Personal allergy Day-care diseases attendance
8 –
7 –
6 –
5 –
4 –
3 –
2 –
1 –
0
Terapia di mantenimento nel wheezing prescolare:in base a cosa decidere?
What drives prescribing of asthma medication to preschool wheezing children? Montella, Pediatr Pulmonol 2013
376 pts (32.8 mo) with wheezing (54% frequent wheeze: ≥ 4 episodes/yr)
77% 23%
ED visi
ts
Hospit
al ad
miss
ions
Previo
us b
ronc
hioliti
s
Noctu
rnal
arou
sals
0%
50%
100%
Not treated Treated
Frequenza e severità dei
sintomi sono i principali
determinanti nella decisione dei pediatri di libera scelta di trattare o non
trattare a lungo termine
p < 0.05
p = NS
23% 77%
What drives prescribing of asthma medication to preschool wheezing children? Montella, Pediatr Pulmonol 2013
Eur Respir J. 2014
Novità nella Terapia delle Malattie Respiratorie
• Tosse
Duration of symptoms of respiratory tract infections in children: systematic review. Thompson, BMJ. 2013
Days
Resolution of acute cough
in 50% of ch. at 10 days
10%: cough at 25 days
50
%
10
Starting point for treatment of cough: Medical History
Acute (< 3 wks)
Recurrent acute (≥ 2/yr; 7-14 days) Chronic (> 8 wks)
Prolonged acute (subacute; 3-8 wks)
Marais, ADC 2005
ACUTE and SUB-ACUTE
CHRONIC
RECURRENT
Therapy for cough should be directed at the aetiology and specific treatments used
where possible Chung, Pulm Pharmacol Ther 2002
ACUTE COUGH
Foreign Body urgent rigid bronchoscopy
HOW TO TREAT?
EZIOLOGIA
specifica se ne è chiaramente identificabile la causa (ad es. se associata a caratteristiche suggestive di una patologia polmonare o sistemica)
non specifica quando è isolata, senza evidenza di altri sintomi respiratori ed associata a rx- torace nella norma Shields, Thorax 2008
Respiratory tract infection Non Specific Cough.
Honey, Dextromethorphan (DM), and No Treatment on Nocturnal Cough for Coughing children and Their Parents. Paul, Arch Pediatr Adolesc Med 2007
Honey may be preferable for cough and sleep difficulty in URTI
105 ch. with URTI & night cough
Honey DM No therapy
Cough frequencyFirst nightSecond night
p<0.001
-1. 9 -1.4- 0.9
Scor
e
Over-The-Counter (OTC) drugs
Decongestionants Expectorans
Antihistamines AntitussivesDextromethorphan Codeine
Non drugs (honey)
Treating cough and cold: Guidance for caregivers of children and youth. Goldman, Paediatr Child Health 2011
Fluid intake Mainstay of therapy Humidified air, Echinacea, Zinc, Vitamin C Frequently used, not recommended Non steroidal anti-inflammatory drugs Not significantly reduce symptom score/duration may affect discomfort caused by the viral illness Antihistamines No clinically significant effect Honey Pasteurized honey safe in > 1 yr Demulcent/antioxidant/antimicrobial effects/increases cytokines
2010
Azione
antiossidante
antiinfiammatoria
anestetica
antinfettiva
Mucolitici
• Controindicazione in età < 2 aa (aumento di tosse/muco, dispnea, vomito)*
• Per età > 2 aa, l'uso di un mucolitico è possibile, ma non va continuato in caso di persistenza o peggioramento dei sintomi.
• Alcune significative misure in grado di dar sollievo: Far dormire in posizione supina, con la testa sollevata Far bere il bambino frequentemente Tenere fresca la stanza Non fumare in casa, anche al di fuori della camera
•Acetilcisteina, carbocisteina, ambroxolo, bromexina,
sobrerolo, neltenexina, erdosteina, telmesteina *
•Farmaci uso rettale con derivati terpenici (es, canfora, timo, terpineolo, mentolo, olii di aghi di pino, eucalipto e trementina): NO < 30 mesi e se epilessia/conv. febbrili)
Novembre 2010
Mucolitici per uso orale/rettale
Upper Airway Cough Syndrome (UACS) in Children
• Includes various types of rhinosinus diseases that induce cough (allergic/nonallergic rhinosinusitis; tonsillar hypertrophy)
• Antihistamines/ nasal steroids + allergen avoidance(= allergic rhinitis)
• Resolution can take up to 2- 4 wks of therapy Goldsobel, J Pediatr 2010
PROLONGED ACUTE (SUBACUTE) COUGH3-8 wks
Chest 2006 Thorax 2008
CHRONIC COUGH
Chronic sinus disease?Protracted Bacterial
Bronchitis?
•SPECIFIC COUGH
Protracted Bacterial Bronchitisin which patients?
Preschool healthy children with significant viral LRT infections
• H. influenzae
• S. pneumoniae
• M. catarrhalis
• P. aeruginosa
Priftis, Chest 2013
Chronic wet cough ≥ 4 wks in the absence of other diagnoses
Persistent symptoms + intermittent exacerbations
Impairment of host defenses and impaired mucociliary clearance
CILIA CHANGES RECOVERY AFTER MANY WEEKS
CHEST IMAGING
• Normal lung (30%) • Bronchial wall thickening (48%)• Increased bronchial markings (20%)• Consolidation (14%)
Narang, PLoS One. 2014
Chronic SinusitisOral antibiotic therapy Scadding, CEA 2007
Protracted Bacterial Bronchitis (PBB)
Oral antibiotic therapy + Chest physiotherapy Priftis, Chest 2013
Kompare, J Pediatr 2012
CHRONIC COUGH
• Infezioni
Novità nella Terapia delle Malattie Respiratorie
1. Clinicians should not administer salbutamol2. Clinicians should not administer epinephrine3. Nebulized hypertonic saline should not be administered in the ED4. Clinicians may administer nebulized hyper. saline (3%) in hospital5. Clinicians should not administer systemic steroids in any setting6. Clinicians may choose not to administer O2 if SaO2 > 90%7. Clinicians may choose not to use continuous pulse oximetry8. Clinicians should not use chest physiotherapy9. Clinicians should not administer antibacterial medications to infants
and children unless there is a concomitant bacterial infection, or a strong suspicion of one
10. Clinicians should administer nasogastric or intravenous fluids for infants who cannot maintain hydration orally
Pediatrics. 2014 Nov
Not receiving therapy
Receiving therapy0
0.5
1
1.5
Strepto Staphylo Veillonella Rothia
Changes in gastric and lung microflora with acid suppression. Rosen, JAMA Pediatr. 2014 Oct
5yr prospective study of 99 pts 1-18 yrs (cough at least 3 times/wk for at least 1 month broncho/gastroscopy; 48% acid suppressed)
p < 0.05
Gastric bacterial concentrations, log10
CFU/ml
Bacillus; Dermabacter; Lactobacillus; Peptostreptococcus; Capnocytophaga;Propionibacterium
Positive correlations between proximal nonacid reflux & lung bacterial concentrations (r 0.5!)
Lu
ng
Gastric flora can influence lung flora through nonacid GER in acid-suppressed patients
Acid suppression may need to be limited in patients at risk for infections
Oral Amoxicillin: 1° choice: effective, tolerated, cheap Alternatives: co-amoxiclav, cefaclor, macrolides
Macrolides: -add if no response to 1st line therapy after 48 h
(see severity assessment)
-use if Mycoplasma/Chlamydia is suspected
Pediatric CAP: which antibiotic should be used?
Thorax 2011, CID 2011
Parenteral therapy Preferred: intravenous azithromycin(10 mg/kg on days 1 and 2 of therapy;transition to oral therapy if possible)
Alternatives: intravenous erythromycin lactobionate(20 mg/kg/d every 6 hours)
Oral therapy (step-down therapyor mild infection)
Preferred: azithromycin (10 mg/kg on day 1, followed by 5 mg/kg/d once daily on days 2–5)
Alternatives: clarithromycin(15 mg/kg/d in 2 doses) or oral erythromycin (40 mg/kg/d in 4 doses);
INPATIENTS Management of Atypical Bacteria
Macrolides at least x 14 days (azithro 5 days)
OUTPATIENTS
CID 2011
Erythromycin interacts with motilin receptors, induces strong gastric and pyloric bulb contractions infantile hypertrophic
pyloric stenosis (3 to 12 wks old infants: 1-2 %o births)
5 giorni di terapia per un bambino di 15 Kg: claritromicina ~ € 16 azitromicina ~ € 22 eritromicina ~ € 10
PEARLS
Use of macrolides in mother and child and risk ofinfantile hypertrophic pyloric stenosis. Lund BMJ 2014.
Erythromycin is associated with hypertrophic pyloric stenosis risk, but no certainty about other macrolides (pertussis !!!!!)
A comparative clinical study of macrolide-sensitive and macrolide-resistant Mycoplasma p. in pediatric patients.
Matsubara J Infect Chemother 2009.
68% macrolide-sensitive
32%
macrolide-resistant
Efficacy of macrolide therapy 91.5% for macrolide sensitive 22.7% for macrolide resistance (p < 0.01)
In children increasing prevalenceof macrolide-resistant M. pneumoniae
More prolonged fever (> 48 hr) and cough
Macrolide sensitive
Macrolideresistent
Fever days 1.5 4.0
Cough days 7.0 11.4
Frequency of the A2063G mutation in 23S rRNA gene [significantly >> in children (61.3%) than adults (13.3%)]
Yoo, Antimicrob Agents Chemother. 2012
The resistance
30 ch. with Mycoplasma (PCR + serology)
70% resistant (fever)After minocycline,
fever disappeared (48 h)
Antibiotic Management of Atypical Bacteria
Mycoplasma (DNA copies)
KawaiRespirology. 2012
Clinical Relevance of Mycoplasma macrolide resistance Cardinale, J Clin Microbiology 2013
Levofloxacin in macrolide resistant M. pneumoniae
Oral therapy (step-down therapyor mild infection)
INPATIENTS Management of Atypical BacteriaPreferred: intravenous azithromycin(10 mg/kg on days 1 and 2 of therapy;transition to oral therapy if possible)
Alternatives: intravenous erythromycin lactobionate(20 mg/kg/d every 6 hours) or levofloxacin(16-20 mg/kg/d every 12 hours; maximum dailydose, 750 mg)
OUTPATIENTS
Parenteral therapy
Preferred: azithromycin (10 mg/kg on day 1, followed by 5 mg/kg/d once daily on days 2–5)
Alternatives: clarithromycin(15 mg/kg/d in 2 doses) or oral erythromycin (40 mg/kg/d in 4 doses);for children >7 yrs old, doxycycline(2–4 mg/kg/day in 2 doses; for adolescents with skeletal maturity, levofloxacin (500 mg) or moxifloxacin (400 mg)/dCID 2011
WARNING
Bacteria acquire macrolide resistance very fast if used indiscriminately (especially the second-generation agents)
Lancet 2007 Eur Respir J 2010
S. pneumoniae resistance to macrolides
Italy 34% (range, 25-50%)
Southern Italy >70%www.ecdc.europa.eu (2012)
Resistenza S. pneumoniae ai macrolidi in Campania (2012)
TUTTI I MATERIALI: 61.7% SANGUE e LIQUOR: 63% RESPIRATORI: 61.7%
AR-ISS: sorveglianza antibiotico-resistenza in Italia Rapporto del triennio 2006-2008
Gram-negativi : ↑↑ resistenza E. coli: fluorochinoloni K. pneumoniae: Italia: 36%!! cefalosporine III^ gen. (37%) fluorochinoloni
Can Resistance to AntibioticsBe Minimized?
Recommendations
1. Limit the spectrum of activity of antimicrobials to that required to treat the identified pathogen.
2. Use the proper dosage of antibiotics to achieve a minimal concentration to decrease risk of resistance.
3. Treat for the shortest effective duration to minimize exposure of both pathogens and normal microbiota to antimicrobials.
4. Limit exposure to any antibiotic.
Sinusitis and Pneumonia Hospitalization After Introduction of PCV. Lindstrand, Pediatrics. 2014 Nov 10
PCV7PCV13 PCV13PCV7
PCV7 and PCV13 prevent
pneumonia at preschool age
If discovery of new antibiotics continues to falter while resistance to drugs continues to spread, society’s medicine chest will soon lack effective treatments for many infections. Nathan, Sci Transl Med. 2012
TAKE HOME MESSAGE