1. Lower Respiratory Tract Infections Méhes Leonóra, MD Department of Infectious and Pediatric Immunology 2012.11.07

2. LRTI - Bronchiolitis viral infection severe symptoms - young infants, < 2 y, peak: infants aged 3-6 months self-limiting condition, RSV Other causes: parainfluenza, Influenza B, echovirus, Rhinovirus, Adenovirus, Mycoplasma Cough, dyspnea, wheezing, poor feeding, hypothermia or hyperthermia Th: humidified oxygen, nebulized epinephrin, mechanical ventillation, bronchodilator, corticosteroid, ribavirin

3. CAP Typical bacterial pathogens: Streptococcus pneumoniae (penicillin-sensitive and -resistant strains), Haemophilus influenzae (ampicillin- sensitive and -resistant strains), Moraxella catarrhalis (all strains penicillin-resistant) CAP is usually acquired via inhalation or aspiration of pulmonary pathogenic organisms Aspiration pneumonia is the only form of CAP caused by multiple pathogens (eg, aerobic/anaerobic oral organisms). Patients with CAP who have impaired splenic function may develop overwhelming pneumococcal sepsis, potentially leading to death within 12-24 hours, regardless of the antimicrobial regimen used.

4. Diagnosis Sputum Gram stain Blood culture Blood tests: liver, renal function, CBC, ESR, CRP level Hypophosphataemia + hematuria – Legionellosis Cold agglutinin level – Mycoplasma Serology: Clamydia, Mycoplasma, Legionella Periferal smear: impaired splenic function: Howell-Jolly bodies Urinary antigen test: S.pneumoniae, Legionella serotype I (80%) Chest X-ray, CT scan Bronchoscopy: BAL

5. Staphylococcus aureus: secondary to influenza ICU: polymicrobial infections (K.pneumoniae, P.aeruginosa) gram-negative pathogens (eg, Enterobacter species, Serratia species, Stenotrophomonas maltophilia, Burkholderia cepacia) rarely cause CAP. Atypical pneumonia: zoonotic atypical: Chlamydia psittaci, Francisella tularensis, Coxiella burnetii (Q fever). Nonzoonotic atypical: Legionella species, M pneumoniae, Chlamydia pneumoniae -15% of all CAP cases

6. a variety of pulmonary and extrapulmonary findings (eg, CAP plus diarrhea) bacterial CAP: fever, productive cough, pleuritic chest pain. atypical CAP: subacute, 1 or more extrapulmonary features Legionella pneumonia: productive or nonproductive cough M pneumoniae or Chlamydia pneumoniae: nonproductive cough. Zoonotic CAP: patients with tularemia have had recent close contact with rabbits or have recently been bitten by a tick.

7. Etiology - microbi S. pneumoniae inf multiple letality >> Mycoplasma pneumoniae inf Streptococcus pneumoniae etiol not excluded Mycoplasma pneumoniae,Chlamydophila pneumoniae: macrolid, doxycyclin, fluoroq Legionella pneumophila: macrolid, fluoroq S. pneumoniae strains 95 %: ampicillin/amoxicillin, cephalosporin (cefuroxim, cefotaxim, ceftriaxon), carbapen (ertapenem, imipenem, meropenem) 3rd gen levofloxacin, 4th gen moxifloxacin (resp fluroq) good spectrum against S. pneumoniae macrolid derivatives S. pneumoniae efficacy the same multiresistant G - microb, S.aureus

8. Risk factors S. pneumoniae - 40%, childhood, elderly, severe basic disease Young adult: Mycoplasma pneumoniae elderly, with risk factors: G - bacilli (Haemophilus influenzae, E. coli, Klebsiella pneumoniae) Aspiration pneumonia viral pneumonia – immunocompetent, spontaneously healed Poor prognosis: elderly (>65 y) basic diseases chronic cardio-pulmonary hepatic, renal insufficiency neoplasiaimmunodeficiency diabetes mellitus smoker

9. Scoring systems CURB65: Confusion, Urea, Respiratory rate, Blood pressure (systolic value  90, diastolic value  60 mmHg), 65 (y) CRB65 – each 1 point 0 - moderately severe status, mortality rate <3%, ambulantory th 1-2 - severe st, mort. rate 10%, 2 p = hospitalization 3-4 - very severe st, mort rate 15-40%, ICU treatment

10. Criteria of severe pneumonia Major criteria (first visit): mechanical ventillation vasopressor therapy (> 4 hours) (septic shock) Minor criteria (first visit): Respiration rate  30/min Severe respiratory insuff. (PaO2/FiO2  250) multilobular infiltrate - desorientation - uraemia - leucopenia - thrombocytopenia - hypothermia - aggressiv fluid supplementation, hypotension 1 major or 3 or more minor criteria

11. Treatment severe septicaemia, septic shock – first ab dosis within 1 hour Sample taking for microbiological exam. Efficacy of the chosen ab – severity of clinical situation Parenteral administration, sequential therapy Deescalation Length of treatment: good response to th: 7-10 days (radiol. positivity for weeks) legionellosis treament: 3 w

12. Treatment Typical +atypical coverage Monotherapy: doxycyclin, resp quinolons, tigecyclin Combination: Ceftriax + doxyc/ azithro / resp quinolon 12-14 day sequential therapy: iv – oral Avoid empiric macrolide monotherapy: 25% of S pneumoniae strains are naturally resistant to all macrolides Monotherapy: doxycycline/ resp quinolone highly penicillin-resistant S pneumoniae infections: beta lactams, doxycycline, respiratory quinolones Very highly penicillin-resistant S pneumoniae (MIC 6 µg/mL): ceftriaxone Chest X-ray: after 1 week

13. Empirical ab gr.1 Ambul treat pn: < 65 y, without any basic disease CRB65 score = 0 amoxicillin (min 3 g/d) or macrolid or doxycyclin penicillin allergy: resp fluoroq macrolid deriv monotherapy No improvement within 48 h, chest X ray, lab parameters Resp fluoroq (levofloxacin, moxifloxacin)

14. Empir th gr. 2 Ambul treat pneumonia: basic disease a/o > 65 y CRB65 score =1 amoxi/clav, cefuroxim +/- macrolid or resp fluoroq (levofloxacin, moxifloxacin) parent th: ceftriaxon, cefuroxim +/- macrolid - letal: < 5 %, finally 20 % hospit - hospit decision within 48 h

15. Empir th gr. 3 CAP + hospit CRB65 score = 2 amoxi/clav, cefuroxim, ceftriaxon/cefotaxim + macrolid or resp fluoroq Empir ab: atypical microbi multires G - bacil, ESBL+ Klebsiella spp., E.coli - ertapenem P.aeruginosa: imipenem, meropenem, doripenem, ceftazidim, cefepim – an.: bronchiectasia, severe COPD, cystic fibrosis steroid th: controversial, no effect on prognosis, no evidence based th efficacy

16. Empir th gr. 4 Severe, ICU CRB65 score = 3 – 4 1. Pseudomonas aeruginosa low incidence: ceftriaxon/cefotaxim, carbapenem (ertapenem), pip/tazo + macrolid or resp fluoroq 2. Pseudomonas aeruginosa possible Ceftazidim, carbapenem (imipenem, meropenem), pip/tazo + ciprofl or beta-lact + aminogl + macrolid or resp fluoroq G – bacil: diabetes mellitus, COPD, alkoholism levofloxacin higher dose: Streptococcus pneumonia, Pseudomonas aeruginosa, Klebsiella pneumoniae (750-1000 mg/nap) aspir pneumonia: anaerob spectrum (not metronidazol)

17. Influenza prim/sec pneumonia Outbreak period influenza A és B virus early pn within 48 h: oseltamivir, zanamivir Primary viral pneumonia: rapid hospital, spec antivir, antibact th Spec antivir th: oseltamivir 2x75 mg/d per os + amoxi/clav or ceftriaxon or moxifloxacin or levofloxacin Secondary, bacterial pneumonia: Streptococcus pneumoniae, Staphylococcus aureus moderately severe: amoxi/clav 3x1,2 g/d (iv) severe: ceftriaxon 2 g/d or moxifloxacin 400 mg/d or levofloxacin 500-1000 mg/d

18. Vaccination Pneumococcal vaccines: prevent pneumococcal bacteremia but not necessarily pneumococcal pneumonia Prevenar: 13-valent conjugate vaccine, children aged 6 weeks to 5 years 23-valent vaccine (Pneumovax 23) is approved for adults aged 50 years or older and persons aged 2 years or older

19. Thank you for your attention!